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Nikolaos Nikolaou

BSc (Hons), MSc (Distinction), DPhil

Postdoctoral Researcher

My current research focuses on the role of pre-receptor regulation of steroid hormone action and bile acid synthesis through manipulation (genetic and pharmacological) of expression and activity of the A-ring reductases (5α-reductase and 5β-reductase) that have the ability to regulate steroid and bile acid availability within human liver. Steroid hormones, including glucocorticoids, androgens and oestrogens are potent regulators of metabolic phenotype, both in vitro and in vivo. Glucocorticoid excess has been associated with hepatic steatosis and it has been shown that metabolism of cortisol changes across the NAFLD disease spectrum. In addition, there is increasing evidence of the ability of bile acids to potently regulate multiple aspects of the metabolic phenotype, through multiple receptors including the farnesoid-X-receptor (FXR), the membrane receptor G-protein-coupled bile acid receptor 5 (TGR5), the constitutive activated receptor (CAR) and the pregnane-X-receptor (PXR). My work tests the hypothesis that manipulation of expression and activity of the A-ring reductases can regulate aspects of the metabolic phenotype within human hepatocytes. The in vitro techniques I employ include human hepatoma cell culture, genetic manipulation of the A-ring reductases (over-expression, siRNA silencing), gene expression, western blotting, functional activity assays (e.g. ELISAs, GCMS of lipid metabolites/urinary steroids), RNA sequencing and high throughput enzyme assays.